The Bogalusa Heart Study is a long-term, epidemiologic program concerned with the early natural history of arteriosclerosis (atherosclerosis and essential hypertension) in a total biracial (black- white)childhood population, now reaching 20-41 years of age. The proposed research focuses on physiologic, genetic and lifestyle factors that contribute to cardiovascular (C-V)disease. The specific aims of the proposal are to study: 1) the impact of genetic factors on the evolution from childhood C-V risk factors to subclinical (C- V structural and functional characteristics) and clinical morbidity in adult population followed over a long period of time; and 2) the association of risk factor phenotypes to anatomic changes in the C- V system as seen by necropsy. The population for genotype- phenotype studies include approximately 1,400 siblings (sibships greater than 2) derived from 17 longitudinal birth cohorts. The C- V phenotypes include obesity measures, blood pressures, lipids, lipoproteins and apoproteins, homocysteine, glucose-insulin, fibrinogen, plasminogen activator inhibitor-1 and von Willebrand factor. The environmental risk factors consist of sociodemographic characteristics, tobacco and alcohol use, oral contraception, physical activity and diet. Subclinical morbidity will include echo-Doppler measurements of cardiac-carotid structure and function. Using robust sibling pair linkage methods, a genome-wide searching involving 391 markers with spacing of 10cM will be conducted for genes which influence quantitative traits. This will be supplemented with 41 highly polymorphic markers located in or near candidate genes likely to be related to obesity, lipoprotein metabolism, blood pressure levels, insulin resistance, diabetes, atherogenesis and thrombosis. Emphasis will be placed on longitudinal changes of clustering of correlated traits, i.e., insulin- resistant syndrome, Syndrome X. Analyses will be conducted to assess whether the same genes exert significant effects in both blacks and whites. Autopsy studies will address relationship of antemortem risk factors with the development of anatomic atherosclerotic and hypertensive lesions. The proposed studies will enable development of rational prevention programs.